A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation

NCT ID: NCT02719782

Last Updated: 2018-11-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-02
• Study Completion Date: 2019-12-31

Brief Summary

Hepatocellular carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 10 patients with Hepatitis B virus (HBV) related HCC who underwent liver transplantation and are confirmed to have recurrent HCC. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.

Detailed Description

This is a phase I, single armed and open labelled trial in patients with recurrent HBV related HCC after liver transplantation. Subjects who meet eligibility criteria will receive escalating doses of HBV specific T cell receptor (TCR-T) on Day 1, Day 8, Day 15 and Day 22 of the first 28-day treatment cycle, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of repeated cycle. A 21-day treatment break will be given between each cycle. Treatment will be continued until disease progression unless otherwise specified per investigator's discretion. Subjects will be followed up post treatment for safety monitoring, including monthly follow up for the first three month and every 2-monthly follow up up to 24 months post treatment.

Conditions

Recurrent Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HBV/TCR T cell Infusion

This is a single-arm study.

Patients will receive a total of 2 cycles, in which first 28-day treatment cycle consists of escalating doses of TCR-T on Day 1, Day 8, Day 15 and Day 22, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of second (final) cycle. A one month treatment break will be given between the cycles.

Group Type: EXPERIMENTAL

Biological: TCR-T

Intervention Type: BIOLOGICAL

Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Interventions

Biological: TCR-T

Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Diagnosis as hepatocellular carcinoma (HCC)
• Underwent liver transplantation and confirmed recurrent HCC post operation
• Seropositive for hepatitis B surface antigen
• No major post-operative complication
• Life expectancy of at least 12 weeks
• Ability to provide informed consent
• Ability to comply with study procedures
• HLA profile matching with HLA-class I restriction element of the available T cell receptors

Exclusion Criteria

• Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR-T, stem cells or combined therapy of the kind within 3 months prior to enrolment
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
• Likelihood to require steroid treatment during the period of the clinical trial
• Any other concurrent liver infections such as hepatitis A, C or D infection
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• Known Central Nervous System tumours including metastatic brain disease.
• Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
• Patients with reproductive potential who tested positive for serum or urine pregnancy test result within 14 days prior to enrolment.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agency for Science, Technology and Research

OTHER

Sponsor Role: collaborator

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Lion TCR Pte. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qi Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Third Affiliated Hospital, Sun Yat-Sen University

Antonio Bertoletti, MD

Role: STUDY_CHAIR

Duke-NUS Graduate Medical School

Locations

Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Grace Khoo Koay

Role: CONTACT

clinicaltrials@liontcr.com

(65) 69260818

Xiaofang Zheng

Role: CONTACT

86-(020)-8217-9791

Facility Contacts

Qi Zhang, Ph.D, MD

Role: primary

(86)20-85253106

References

Qasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.

Reference Type: BACKGROUND

PMID: 25308176 (View on PubMed)

Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.

Reference Type: BACKGROUND

PMID: 21145860 (View on PubMed)

Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.

Reference Type: BACKGROUND

PMID: 23941866 (View on PubMed)

Yang F, Zheng X, Koh S, Lu J, Cheng J, Li P, Du C, Chen Y, Chen X, Yang L, Chen W, Wong RW, Wai LE, Wang T, Zhang Q, Chen W. Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial. Hepatol Int. 2023 Aug;17(4):850-859. doi: 10.1007/s12072-023-10524-x. Epub 2023 Apr 17.

Reference Type: DERIVED

PMID: 37067675 (View on PubMed)

Other Identifiers

LTCR-HCC-2-1

Identifier Type: -

Identifier Source: org_study_id